Novel Pepsin Test Better to ID Aspiration Reflux

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A molecular test that detects pepsin in bronchoalveolar lavage (BAL) fluid was a more sensitive biomarker of aspiration-associated reflux disease in children with chronic pulmonary disease than the most widely used test, lipid-laden macrophages.

Point out that pepsin was not found in samples from any of the controls without reflux or other respiratory symptoms, suggesting that it may prove to be a more sensitive and specific assay than currently available tests.

A molecular test that detects pepsin in bronchoalveolar lavage (BAL) fluid was a more sensitive biomarker of aspiration-associated reflux disease in children with chronic pulmonary disease than the most widely used test, according to a new study.

Using the experimental assay, researchers identified pepsin in BAL specimens from 74% of children with pulmonary disease who underwent bronchoscopy and 71% of those with a tracheostomy, while the presence of lipid-laden macrophages (LLMs) was found in 91% of the bronchoscopy patients and 52% of the tracheostomy group.

Even more significant, no BAL specimens from a control group of healthy children were positive for pepsin, while 64% of the specimens were positive for LLMs, researcher Elizabeth A. Kelly, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote online in JAMA Otolaryngology-Head & Neck Surgery.

"Patients with chronic pulmonary disease have a high prevalence of aspiration-associated extra-esophageal reflux disease (AERD), which may have important treatment implications," the researchers wrote. "The presence of pepsin was a better predictor of AERD in patients with respiratory symptoms compared with controls than the presence of LLMs."

Reflux aspiration as well as direct aspiration of ingested material have both been implicated in the development and progression of pulmonary disease, but distinguishing between the two remains problematic.

Lipid-laden alveolar macrophages have been shown to be present in BAL samples from patients with lung disease and gastroesophageal reflux, but LLMs are also routinely found in people without these conditions so it is not a particularly sensitive predictor of aspiration, the researchers noted.

Despite this drawback, measurement of LLMs in BAL specimens is a commonly used test to identify AERD.

"Pepsin is a protein that is only found in one place in the human body, and that is the stomach," Medical College of Wisconsin professor of otolaryngology and communication sciences Joseph E. Kerschner, MD told MedPage Today. "So when we find it in the lung contents, as we did with many chronically ill patients, it means that they are aspirating stomach content into their lungs."

The study by Kelly, Kerschner, and colleagues included 34 pediatric patients with chronic pulmonary disease who underwent bronchoscopy, 31 pediatric patients with a tracheostomy, and 11 pediatric controls without a history of respiratory symptoms or gastroesophageal reflux undergoing elective surgical procedures.

In the bronchoscopy group, 16 patients had chronic respiratory symptoms, 10 had recurrent pneumonia, and the rest had other respiratory symptoms. The tracheostomy group included 15 patients with the procedure performed for anatomic abnormalities, nine who had neuromuscular disease, and seven who had the procedure performed for other reasons.

BAL samples were obtained using flexible bronchoscopy under general anesthesia and the samples were tested for pepsin and LLMs.

Around half of the patients in the bronchoscopy group were receiving drug treatments for reflux, including H2 blockers, proton pump inhibitors and/or metoclopramide. About 60% of the tracheostomy patients were receiving drug treatments for the condition.

The finding of pepsin in the BAL specimens of more than 70% of patients in the two chronic pulmonary disease groups suggests that the frequency of AERD is underestimated in these patients, the researchers noted.

Kerschner said this is likely to be the case in adult chronic pulmonary disease patients as well as children.

The fact that pepsin was not found in samples from any of the controls without reflux or other respiratory symptoms suggests that it will prove to be a more sensitive and specific assay than currently available tests, he added.

The researchers are in the planning phase of a clinical trial that will include adults as well as children, and they hope to develop the pepsin test as a commercially available assay for aspiration-associated reflux.

One unanswered question is whether the pepsin test will help clinicians devise better treatment plans for their patients.

"The next step is to determine if this assay can be used to improve treatment outcomes," Kerschner said.

Children's Hospital and Health System Foundation provided funding for the collection, management, and analysis of the data. Statistical support and interpretation of the data were supported by grants from the Clincal and Translational Science Award program of the National Center for Research Resources.

Nikki Johnston, PhD, reports being a consultant for Koufman Diagnostics LLC. No other disclosures were reported by the researchers.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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